SepsisPhase 2REVISTA-DOSENCT04999137
Evaluation of Safety and Dosing of a Vitamin C Bundle for Sepsis Treatment in Africa
A Phase 2 study testing Vitamin C and Vitamin B1 in people with Sepsis and Septic Shock, run by Liverpool School of Tropical Medicine at 2 sites in Uganda.
Trial summary
Open-label phase 2a Randomized Controlled Trial (RCT) assessing the pharmacokinetics of two different doses of intravenous vitamin C given alongside vitamin B1 in adult medical patients with sepsis and hypotension. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis, Septic Shock, HIV
- What is being tested?
- Vitamin C and Vitamin B1
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 2 sitesUganda
- Study dates
- 1 Sep 2021to 29 Dec 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult (≥18 years old) patients presenting to the emergency department of Kiruddu National Referral Hospital (KNRH) with:
- suspected infection [(any of): temperature >38 degrees Celsius or <36 degrees Celsius or (in the past seven days) fevers, rigors, night sweats or antibiotic use]; AND
- systolic blood pressure (SBP) <90 mmHg
- Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study.
- Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
Who cannot join
- Pregnant or known active breast feeding
- Non-severe, localized, uncomplicated infection (e.g., cellulitis with only local symptoms) which is apparent on clinical examination
- Severe bleeding or hemorrhagic shock
- Hypotension likely secondary to a cause other than sepsis or sepsis-induced cardiac insufficiency
- Detainee or prisoner
- Admission to a surgical or obstetric/gynecological ward
Show all 14Show fewer
- Emergency surgery required
- Previously recruited to the REVISTA-DOSE study
- History of end stage renal disease requiring dialysis
- Current symptomatic renal stones or or a previous diagnosis of primary hyperoxaluria or oxalate nephropathy
- History of allergic reactions to vitamin C or vitamin B1
- Use of vitamin C at a dose greater than 1 g (oral or intravenous) within 24 hours of screening
- Chronic disease/illness that, in the opinion of the site investigator, has a lifespan of less than 30 days unrelated to current sepsis diagnosis (e.g., advanced malignancy or neurodegenerative disease).
- Previous or current enrolment in a trial in which co-enrolment is not allowed
Trial locations and contacts
2 sites in 1 country.
Uganda2 sites, 2 recruiting
- Recruiting
Infectious Diseases Institute, Makerere University
Kampala
Christine Sekaggya-Wiltshire, MMed PhD, +256772479791, csekaggya@idi.co.ug
- Recruiting
Kiruddu National Referral Hospital
Kampala
Priscilla Haguma, MMed MS, +256777272582, priscilla.haguma@walimu.org
Sharon Nyesiga, MMed, +256775661159, sharon@walimu.org
About this study
Official title: Evaluation of Pharmacokinetics, Safety and Feasibility for Administration of Two Doses of Intravenous Vitamin C Combined With Vitamin B1 for the Management of Adult Patients Admitted With Sepsis to Kiruddu National Referral Hospital
Open-label phase 2a Randomized Controlled Trial (RCT) assessing the pharmacokinetics of two different doses of intravenous vitamin C given alongside vitamin B1 in adult medical patients with sepsis and hypotension.
Read the detailed description
Sepsis is a life-threatening infection which, due to a dysregulated host response to infection, is responsible for more than 11 million deaths annually, a large percentage of which occur in sub-Saharan Africa (sSA). Emerging research shows promising benefits in treating sepsis patients with "metabolic resuscitation" using combinations of hydrocortisone, intravenous (IV) ascorbic acid (vitamin C) and IV thiamine (vitamin B1), alone or in combination. Studies are currently underway in the USA, Europe, Asia, and South America to understand whether combinations of these medicines or the medicines individually can improve outcomes for patients with sepsis. Although none of these studies are being conducted in sSA, the medicines comprising these metabolic 'bundles' are inexpensive, readily available and relatively safe to administer. It is critical that similar studies are conducted in sSA to evaluate whether or not these inexpensive medicines (or a combination of them) are efficacious for improved survival among patients with sepsis. If these studies prove that these medicines can improve survival from sepsis, there is a large potential to save many lives. Through the Preparation for Randomised Evaluation of a VItamin C bundle for Sepsis Treatment in Africa (REVISTA-Prep) studies, the investigators intend to conduct preliminary research in Uganda to help define parameters for a future RCT aimed at identifying the optimal vitamin C and vitamin B1 combination for improving survival from sepsis among adults in sSA, where resources are constrained, intensive care units are rare and issues like poverty, malnutrition and HIV are common. The study described in this protocol (i.e., REVISTA-DOSE) aims to establish the optimal vitamin C dosing strategy for the future REVISTA-RCT (assessing the efficacy of variations of a treatment bundle comprising vitamin C/B1 and/or hydrocortisone for reducing mortality among adult patients with sepsis in Africa).
- Conditions
- Sepsis, Septic Shock, HIV
- Being tested
- Vitamin C, Vitamin B1
- Keywords
- vitamin c, ascorbate, vitamin b1, thiamine, sepsis, septic shock, hiv, malnutrition
- Medical subject headings
- Sepsis, Shock, Septic, Acquired Immunodeficiency Syndrome, Malnutrition
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin CDrug
Also called Ascor, Ascorbate
Vitamin C (ascor), infused intravenously in 50 mls sodium chloride (NaCl) over 30 minutes every 6 hours for 16 doses
Vitamin B1Drug
Also called Thiamine, Thiamin
Vitamin B1 (200 mg) administered intravenously every 12 hours for 8 doses
| Study group | Role | What they receive |
|---|---|---|
| Intravenous vitamin C 1.5g + intravenous vitamin B1 | Experimental | intravenous vitamin C (1.5 grams) every 6 hours for 16 doses in combination with intravenous vitamin B1 (200 mg) every 12 hours Receives: Drug: Vitamin C; Drug: Vitamin B1 |
| Intravenous Vitamin C 3g + intravenous vitamin B1 | Experimental | Intravenous vitamin C (3 grams) every 6 hours for 16 doses in combination with intravenous vitamin B1 (200 mg) every 12 hours Receives: Drug: Vitamin C; Drug: Vitamin B1 |
| Usual Care | No intervention | Usual care |
What is being measured
The primary outcome is the main question the study is designed to answer.
change in Vitamin C plasma concentration during the intervention period
Vitamin C plasma concentrations will be measured during the intervention period using high-performance liquid chromatography (HPLC) with ultraviolet (UV) analysis and compared to baseline (pre-intervention) concentrations
Measured: during the intervention (days 1-5)
Secondary outcomes (4)
Oxalate excretion in urine
Urine oxalate levels will be measured through two separate 12 hour urine collections.
Measured: during the intervention (hours 0-12 and 72-84)
Incidence of acute hemolysis
Acute hemolysis is defined as:
- hemoglobin drop of at least 2.5 g/dl within 24 hours of a study drug; OR
- reticulocyte count >2 times upper limit of normal at clinical site lab; AND
- at least two of the following:
- haptoglobin < lower limit of normal; ii. indirect (unconjugated) bilirubin >2 times upper limit of normal; iii. lactate dehydrogenase (LDH) >2 times upper limit of normal
Measured: during the intervention (days 0-5)
Enrolment rates
Enrolment rates of patients with sepsis and hypotension
Measured: up to 3 months
Rates of adherence to protocol
Rates of adherence to protocol for treatment, clinical measurements and follow up
Measured: during the intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2021
- Study start1 Sep 2021
- Primary completion29 Dec 2021 (estimated)
- Study completion29 Dec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SepsisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Liverpool School of Tropical Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Infectious Diseases Institute, Uganda, Walimu, University of Copenhagen, University of Liverpool
- Responsible party
- Sponsor
- Investigators
- Shevin T Jacob, MD MPH, Principal investigator, LSTM/IDI/Walimu
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04999137
- Sponsor's protocol ID
- 19-094
- Acronym
- REVISTA-DOSE
- Status last verified
- Sep 2021
- First submitted
- 6 Apr 2021
- Last updated
- 8 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Pharmacokinetics, Safety and Feasibility for Administration of Two Doses of Intravenous Vitamin C Combined With Vitamin B1 for the Management of Adult Patients Admitted With Sepsis to Kiruddu National Referral Hospital
- ClinicalTrials.gov ID
- NCT04999137
- Acronym / sponsor ID
- REVISTA-DOSE / 19-094
- Conditions
- Sepsis, Septic Shock, HIV
- Keywords
- vitamin c, ascorbate, vitamin b1, thiamine, sepsis, septic shock, hiv, malnutrition
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Liverpool School of Tropical MedicineUniversity, hospital or other
- Collaborators
- Infectious Diseases Institute, Uganda, Walimu, University of Copenhagen, University of Liverpool
- Study start
- 1 Sep 2021 (actual)
- Primary completion
- 29 Dec 2021 (estimated)
- Study completion
- 29 Dec 2021 (estimated)
- First posted
- 10 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Open-label phase 2a Randomized Controlled Trial (RCT) assessing the pharmacokinetics of two different doses of intravenous vitamin C given alongside vitamin B1 in adult medical patients with sepsis and hypotension.
Detailed description
Sepsis is a life-threatening infection which, due to a dysregulated host response to infection, is responsible for more than 11 million deaths annually, a large percentage of which occur in sub-Saharan Africa (sSA). Emerging research shows promising benefits in treating sepsis patients with "metabolic resuscitation" using combinations of hydrocortisone, intravenous (IV) ascorbic acid (vitamin C) and IV thiamine (vitamin B1), alone or in combination. Studies are currently underway in the USA, Europe, Asia, and South America to understand whether combinations of these medicines or the medicines individually can improve outcomes for patients with sepsis. Although none of these studies are being conducted in sSA, the medicines comprising these metabolic 'bundles' are inexpensive, readily available and relatively safe to administer. It is critical that similar studies are conducted in sSA to evaluate whether or not these inexpensive medicines (or a combination of them) are efficacious for improved survival among patients with sepsis. If these studies prove that these medicines can improve survival from sepsis, there is a large potential to save many lives. Through the Preparation for Randomised Evaluation of a VItamin C bundle for Sepsis Treatment in Africa (REVISTA-Prep) studies, the investigators intend to conduct preliminary research in Uganda to help define parameters for a future RCT aimed at identifying the optimal vitamin C and vitamin B1 combination for improving survival from sepsis among adults in sSA, where resources are constrained, intensive care units are rare and issues like poverty, malnutrition and HIV are common. The study described in this protocol (i.e., REVISTA-DOSE) aims to establish the optimal vitamin C dosing strategy for the future REVISTA-RCT (assessing the efficacy of variations of a treatment bundle comprising vitamin C/B1 and/or hydrocortisone for reducing mortality among adult patients with sepsis in Africa).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Intravenous vitamin C 1.5g + intravenous vitamin B1 | Experimental | Drug: Vitamin C, Drug: Vitamin B1intravenous vitamin C (1.5 grams) every 6 hours for 16 doses in combination with intravenous vitamin B1 (200 mg) every 12 hours |
| Intravenous Vitamin C 3g + intravenous vitamin B1 | Experimental | Drug: Vitamin C, Drug: Vitamin B1Intravenous vitamin C (3 grams) every 6 hours for 16 doses in combination with intravenous vitamin B1 (200 mg) every 12 hours |
| Usual Care | No intervention | –Usual care |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adult (≥18 years old) patients presenting to the emergency department of Kiruddu National Referral Hospital (KNRH) with:
- Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study.
- Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
Key exclusion criteria (14 listed)
- Pregnant or known active breast feeding
- Non-severe, localized, uncomplicated infection (e.g., cellulitis with only local symptoms) which is apparent on clinical examination
- Severe bleeding or hemorrhagic shock
- Hypotension likely secondary to a cause other than sepsis or sepsis-induced cardiac insufficiency
- Detainee or prisoner
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vitamin CAlso: Ascor, AscorbateVitamin C (ascor), infused intravenously in 50 mls sodium chloride (NaCl) over 30 minutes every 6 hours for 16 doses | Drug | Intravenous Vitamin C 3g + intravenous vitamin B1, Intravenous vitamin C 1.5g + intravenous vitamin B1 |
| Vitamin B1Also: Thiamine, ThiaminVitamin B1 (200 mg) administered intravenously every 12 hours for 8 doses | Drug | Intravenous Vitamin C 3g + intravenous vitamin B1, Intravenous vitamin C 1.5g + intravenous vitamin B1 |
Primary outcome
change in Vitamin C plasma concentration during the intervention period
Time frame: during the intervention (days 1-5)
Vitamin C plasma concentrations will be measured during the intervention period using high-performance liquid chromatography (HPLC) with ultraviolet (UV) analysis and compared to baseline (pre-intervention) concentrations
4 secondary outcomes
Oxalate excretion in urine
Time frame: during the intervention (hours 0-12 and 72-84)
Incidence of acute hemolysis
Time frame: during the intervention (days 0-5)
Enrolment rates
Time frame: up to 3 months
Rates of adherence to protocol
Time frame: during the intervention
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2021.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shevin T Jacob, MD MPH principal investigator
LSTM/IDI/Walimu
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vitamin C and Vitamin B1 in people with Sepsis and Septic Shock, run by Liverpool School of Tropical Medicine at 2 sites in Uganda.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Shevin T Jacob, MD MPH (+256.787.429365, shevin.jacob@lstmed.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
change in Vitamin C plasma concentration during the intervention period (time frame: during the intervention (days 1-5)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Sep 2021.